Deciphering the Threshold and Segmented Nonlinear Association Between Systemic Inflammation Response Index and Spinal Bone Density: Insights From a Large-Scale Population Study

Abstract

Study DesignCross-sectional study.ObjectiveTo examine the association between SIRI and spinal BMD and assess the influence of age, hypertension, and diabetes.MethodsWe analyzed data from 13,950 participants aged ≥20 years. SIRI was calculated using neutrophil, monocyte, and lymphocyte counts, and spinal BMD was measured by DXA. Linear regression, generalized additive models, and segmented regression were used, with subgroup analyses based on age, hypertension, and diabetes.ResultsA threshold effect was observed at SIRI = 0.68. Below this threshold, SIRI negatively correlated with spinal BMD (β = -0.0412, P = 0.0494), while above it, a positive correlation was found (β = 0.0079, P < 0.0001). Subgroup analyses showed stronger positive associations in older adults (≥65 years, β = 0.0136, P < 0.0001), and those with hypertension (β = 0.0089, P = 0.0004) and diabetes (β = 0.0187, P < 0.001).ConclusionA segmented nonlinear relationship exists between SIRI and spinal BMD, with age, hypertension, and diabetes as significant modifiers. SIRI may serve as a biomarker for osteoporosis risk.

Keywords: bone health; inflammation biomarkers; osteoporosis; population-based study; spinal bone mineral density; systemic inflammation response index.

Figure 1.

Flowchart of participant selection and analytical steps.

Figure 2.

Adjusted associations between SIRI and spinal BMD using GAM (A) unadjusted model - The smooth function displays the baseline association between SIRI and spinal BMD without adjustment for any covariates. (B) Minimally adjusted model - Adjusted for basic demographic characteristics, including sex, race, marital status, education level, smoking and drinking status, history of diabetes, and hypertension. Shows the independent effect of SIRI on spinal BMD. (C) Fully adjusted model - Adjusted for all key covariates, including sex, race, marital status, education level, lifestyle factors (smoking and drinking), diabetes and hypertension history, as well as age, weight, height, BMI, WC, TC, HDL-C, LDL-C, and TG, showing the effect of SIRI on spinal BMD with comprehensive variable control.

Figure 3.

Scatter plot of the segmented relationship between SIRI and Spinal BMD (A) Displays the overall association between SIRI and spinal BMD, illustrating the general trend across the full range of SIRI values. (B) Shows the relationship between SIRI and spinal BMD for SIRI values below the identified threshold of 0.68. This segment indicates a slight negative association, aligning with the threshold effect observed in the analysis. (C) Illustrates the association for SIRI values equal to or above 0.68, where a positive relationship between SIRI and spinal BMD becomes evident, supporting the hypothesis that higher SIRI levels are associated with higher spinal BMD values.